Expression of cancer stem cell markers in metastatic melanoma to the brain

Wickremesekera, Agadha; Brasch, Helen D.; Lee, Valerie M.; Davis, Paul F.; Woon, Kelvin; Johnson, Rebecca; Tan, Swee T.; Itinteang, Tinte

doi:10.1016/j.jocn.2018.10.068

Cited by 22 publications

(20 citation statements)

References 24 publications

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“…In the present study, we selected the stem cells derived from human fetal tissue, which have greater clinical therapeutic potential. CD73, CD90, and CD105 are common cell surface markers of mesenchymal stem cells [32], while Oct4 and Sox2 are the classical markers of embryonic stem cells [33]. In this study, positive expressions of CD73, CD90, CD105, Oct4, and Sox2 were observed in hFSSC which indicated that hFSSC presented with the characteristics of both MSC and embryonic stem cell (ESC).…”

Section: Discussionmentioning

confidence: 51%

Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis

Rong

Yang

et al. 2019

Stem Cell Res Ther

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BackgroundRadiation dermatitis is a refractory skin injury caused by radiotherapy. Human fetal skin-derived stem cell (hFSSC) is a preferable source for cell therapy and skin tissue regeneration. In the present study, we investigated the repair effect of using hFSSC secretome on a radiation skin injury model in rats.MethodsWe prepared the hFSSC secretome and studied its effects on the proliferation and tube formation of human umbilical vein endothelial cell (HUVEC) in vitro. Furthermore, we used a Sr-90 radiation-induced skin injury model of rats and evaluated the effects of hFSSC secretome on radiation skin injury in vivo.ResultsThe results showed that hFSSC secretome significantly promoted the proliferation and tube formation of HUVEC in vitro; in addition, hFSSC secretome-treated rats exhibited higher healing quality and faster healing rate than the other two control groups; the expression level of collagen type III α 1 (Col3A1), transforming growth factor β3 (TGF-β3), angiotensin 1 (Ang-1), angiotensin 2 (Ang-2), vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) was significantly increased, while collagen type I α 2 (Col1A2) and transforming growth factor β1 (TGF-β1) were decreased in hFSSC secretome group.ConclusionsIn conclusion, our results provided the first evidence on the effects of hFSSC secretome towards radiation-induced skin injury. We found that hFSSC secretome significantly enhanced radiation dermatitis angiogenesis, and the therapeutic effects could match with the characteristics of fetal skin. It may act as a kind of novel cell-free therapeutic approach for radiation-induced cutaneous wound healing.

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Section: Discussionmentioning

confidence: 51%

Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis

Rong

Yang

et al. 2019

Stem Cell Res Ther

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“…CSCs have been identified in many cancer types, including OCSCC of different subsites, 9 – 11 glioblastoma, 12 renal clear cell carcinoma, 13 primary 14 and metastatic 15 colon adenocarcinoma, and metastatic malignant melanoma. 16 , 17 We have recently reported the presence of 4 CSC subpopulations within human MDHNcSCC: an OCT4 + /NANOG + /SOX2 + /KLF4 + /c-MYC + subpopulation within the TNs, the PTS, the endothelium of the microvessels within the PTS, and an OCT4 + /NANOG − /SOX2 + /KLF4 + /c-MYC + subpopulation solely within the PTS. 27 These CSCs have been suggested as a novel therapeutic target 5 by modulating the RAS.…”

Section: Discussionmentioning

confidence: 97%

“…CSCs have been identified in many cancer types, including oral cavity SCC (OCSCC) of different subsites, 9 – 11 glioblastoma, 12 renal clear cell carcinoma, 13 primary 14 and metastatic 15 colon adenocarcinoma, and metastatic malignant melanoma. 16 , 17 …”

Section: Introductionmentioning

confidence: 99%

Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins

Featherston

Brasch

Siljee

et al. 2020

Plastic and Reconstructive Surgery - Global Open

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Background: Cancer stem cell (CSC) subpopulations within moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNcSCC) express the components of the renin–angiotensin system (RAS). This study investigated the expression of cathepsins B, D, and G, which constitute bypass loops of the RAS, by CSCs in MDHNcSCC. Methods: Immunohistochemical staining was performed on MDHNcSCC tissue samples from 15 patients to determine the expression of cathepsins B, D, and G. Co-localization of these cathepsins with the embryonic stem cell markers Octamer-binding transcription factor 4 (OCT4) and c-MYC was investigated with immunofluorescence staining. Reverse transcription quantitative polymerase chain reaction was performed on 5 MDHNcSCC tissue samples to investigate transcript expression of cathepsins B, D and G. Western blotting and enzymatic activity assays were performed on 5 MDHNcSCC tissue samples and 6 MDHNcSCC-derived primary cell lines to confirm protein expression, transcript expression, and functional activity of these cathepsins, respectively. Results: Immunohistochemical staining demonstrated the expression of cathepsins B, D, and G in all MDHNcSCC tissue samples. Immunofluorescence staining showed localization of cathepsins B and D to the c-MYC+ CSC subpopulations and the OCT4+ CSC subpopulations within the tumor nests and the peritumoral stroma. Cathepsin G was expressed on the tryptase+/c-MYC+ cells within the peritumoral stroma. Reverse transcription quantitative polymerase chain reaction demonstrated transcript expression of cathepsins B, D and G in the MDHNcSCC tissue samples. Western blotting and enzymatic activity assays confirmed protein expression and functional activity of cathepsins B and D in the MDHNcSCC tissue samples and MDHNcSCC-derived primary cell lines, respectively. Conclusions: Cathepsins B, D, and G are expressed in MDHNcSCC with functionally active cathepsins B and D localizing to the CSC subpopulations, and cathepsin G is expressed by mast cells, suggesting the potential use of cathepsin inhibitors in addition to RAS blockade to target CSCs in MDHNcSCC.

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“…Expression of components of the renin-angiotensin system (RAS) by CSCs has been demonstrated in different cancer types including glioblastoma ( 64 ), OCSCC affecting the oral tongue ( 65 ), buccal mucosa ( 66 ), and lip ( 67 ) squamous cell carcinoma (SCC), primary HNcSCC ( 68 ), metastatic colon adenocarcinoma ( 42 ), and metastatic malignant melanoma ( 43 ). This suggests CSCs in these tumors may be targeted by modulation of the RAS ( 12 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…OCT4, SOX2, NANOG, KLF4, and c-MYC act cooperatively to promote pluripotency ( 37 ), and consequently, some or all of these markers have been used to identify CSC subpopulations in many cancer types, including HNcSCC ( 19 ), OCSCC affecting different subsites ( 38 – 40 ), glioblastoma ( 41 ), renal clear cell carcinoma ( 17 ), primary ( 18 ), and metastatic ( 42 ) colon adenocarcinoma, and metastatic malignant melanoma ( 43 , 44 ).…”

Section: Introductionmentioning

confidence: 99%

Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

et al. 2020

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Cancer stem cells (CSCs) have been identified in many cancer types including primary head and neck cutaneous squamous cell carcinoma (HNcSCC). This study aimed to identify and characterize CSCs in metastatic HNcSCC (mHNcSCC). Immunohistochemical staining performed on mHNcSCC samples from 15 patients demonstrated expression of the induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC in all 15 samples. In situ hybridization and RT-qPCR performed on four of these mHNcSCC tissue samples confirmed transcript expression of all five iPSC markers. Immunofluorescence staining performed on three of these mHNcSCC samples demonstrated expression of c-MYC on cells within the tumor nests (TNs) and the peri-tumoral stroma (PTS) that also expressed KLF4. OCT4 was expressed on the SOX2+/NANOG+/KLF4+ cells within the TNs, and the SOX2+/NANOG+/KLF4+ cells within the PTS. RT-qPCR demonstrated transcript expression of all five iPSC markers in all three mHNcSCC-derived primary cell lines, except for SOX2 in one cell line. Western blotting showed the presence of SOX2, KLF4, and c-MYC but not OCT4 and NANOG in the three mHNcSCC-derived primary cell lines. All three cell lines formed tumorspheres, at the first passage. We demonstrated an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation within the TNs, and an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ subpopulation within the PTS of mHNcSCC.

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Expression of cancer stem cell markers in metastatic melanoma to the brain

Cited by 22 publications

References 24 publications

Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis

Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis

Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins

Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

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